Inhibition of gastric emptying and feeding by fenfluramine

To assess the mechanism by which the anorectic agent fenfluramine influences feeding, we examined in Macaca mulatta the effect of intragastric fenfluramine (2 mg/kg) on both feeding and the gastric emptying of saline and glucose test meals. Gastric emptying was measured by the dye-dilution technique, using chronic indwelling intragastric cannulas. The emptying of normal saline was inhibited by fenfluramine as was the initial bolus phase of the emptying of glucose. In contrast, the subsequent controlled phase of glucose emptying was unaffected in two out of four animals, slightly inhibited in one, and strongly inhibited in only one monkey. Rhesus monkeys trained to drink a glucose solution to satiety drank, on average, 21% less after fenfluramine. The emptying of the consumed glucose solution from the stomach was reduced by 39%, whereas gastric volume at satiety was reduced by only 10%. The reduction of intake was strongly related to the degree of inhibition of gastric emptying. These results support an important role for the inhibition of gastric emptying in fenfluramine-induced suppression of feeding.

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Effects of Met-enkephalin and naloxone on gastric emptying and secretion in rhesus monkeys

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1983.245.2.g196 ◽

1983 ◽

Vol 245 (2) ◽

pp. G196-G200

Author(s):

P. T. Shea-Donohue ◽

N. Adams ◽

J. Arnold ◽

A. Dubois

Keyword(s):

Gastric Emptying ◽

Receptor Antagonist ◽

Rhesus Monkeys ◽

Endocrine Cells ◽

Chloride Ion ◽

Opiate Receptor ◽

Sodium Ion ◽

Dilution Technique ◽

Gastric Function ◽

Sodium Potassium

Recent studies have demonstrated the presence of enkephalins in gastric neurons and endocrine cells; however, their role in the regulation of gastric function is unknown. The effect of Met-enkephalin (MET), the stable analogue of Met-enkephalin [D-Ala2]Met-enkephalinamide (DMET), and the opiate receptor antagonist naloxone were studied in five chair-adapted rhesus monkeys. A dye-dilution technique was used to determine simultaneously fractional emptying rate, hydrogen, sodium, potassium, and chloride ion output, and fluid output. Both MET and DMET significantly inhibited fractional emptying rate and H+ secretion following an 80-ml water meal. Only MET, however, significantly altered fluid and sodium ion output. Naloxone had no effect on gastric function following the water meal.

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Interactions between gastric volume and duodenal nutrients in the control of liquid gastric emptying

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.4.r997 ◽

1999 ◽

Vol 276 (4) ◽

pp. R997-R1002 ◽

Cited By ~ 8

Author(s):

Timothy H. Moran ◽

James B. Wirth ◽

Gary J. Schwartz ◽

Paul R. McHugh

Keyword(s):

Gastric Emptying ◽

Adult Male ◽

Rhesus Monkeys ◽

Gastric Volume ◽

Glucose Load ◽

The Relationship ◽

Male Rhesus

We examined the relationships between gastric volume and duodenal glucose load in the regulation of gastric emptying in adult male rhesus monkeys. Intragastric glucose loads (0.125 g/ml) of volumes ranging from 150 to 375 ml empty from the stomach at the same rate from 20 to 120 min. However, to achieve these equivalent emptying rates, progressively larger volumes were emptied in the initial 20 min with increasing gastric volume. Duodenal glucose infusions dose dependently inhibited the 10-min emptying of various volumes of intragastric saline. Although increasing gastric volume resulted in increased emptying, duodenal glucose right-shifted the relationship between initial gastric volume and volume emptied. These data demonstrate that liquid nutrient gastric emptying represents an interaction between gastric volume and nutrient-induced duodenal feedback. For controlled duodenal caloric delivery rates to be established, sufficient nutrient emptying must occur to increase the magnitude of duodenal feedback to withhold a given gastric volume.

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Gastric and duodenal features of meals mediate controls of liquid gastric emptying during fill in rhesus monkeys

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.5.r1282 ◽

1999 ◽

Vol 277 (5) ◽

pp. R1282-R1290 ◽

Cited By ~ 2

Author(s):

Timothy H. Moran ◽

Susan Knipp ◽

Gary J. Schwartz

Keyword(s):

Gastric Emptying ◽

Negative Feedback ◽

Glucose Concentration ◽

Rhesus Monkeys ◽

Physiological Saline ◽

Gastric Volume ◽

Feedback Controls ◽

Lower Glucose ◽

Concentration Dependency

To study the dynamics of liquid gastric emptying in rhesus monkeys under conditions that simulated gastric fill during a meal, we measured the gastric emptying of liquid glucose at various concentrations and volumes when administered intragastrically at rates ranging from 12.5 to 37.5 ml/min. Glucose gastric emptying was faster during than following the period of gastric fill. At a single glucose concentration, volume infused rather than the rate of filling determined the volume emptied. Lower glucose concentrations emptied more slowly than physiological saline. As glucose concentration increased, emptying during fill slowed. Duodenal glucose infusions greatly slowed the rate of saline emptying during fill, demonstrating duodenal feedback control. Although casein hydrolosate emptied more rapidly than glucose, the dynamics of volume and concentration dependency and the role of duodenal feedback were similar. These data reveal that both gastric volume and duodenal negative feedback controls important in gastric emptying following stomach filling also contribute to its control during fill.

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